Assessment of plasma uracil-to-dihydrouracil concentration ratio as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency.

Abstract

OBJECTIVE: To determine and compare the ratio of uracil (U) to dihydrouracil (UH(2)) concentrations in plasma as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency. ANIMALS: 101 client- and shelter-owned dogs. PROCEDURES: Study dogs included 74 clinically normal dogs, 17 dogs with neoplasia, and 10 dogs with renal insufficiency. For each dog, a blood sample was collected into an EDTA-containing tube; plasma U and UH(2) concentrations were determined via UV high-performance liquid chromatography, and the U:UH(2) concentration ratio was calculated. Data were compared among dogs grouped on the basis of sex, clinical group assignment, reproductive status (sexually intact, spayed, or castrated), and age. RESULTS: Mean ± SEM U:UH(2) concentration ratio for all dogs was 1.55 ± 0.08 (median, 1.38; range, 0.4 to 7.14). In 14 (13.9%) dogs, the U:UH(2) concentration ratio was considered abnormal (ie, > 2). Overall, mean ratio for sexually intact dogs was significantly higher than that for neutered dogs; a similar difference was apparent among males but not females. Dogs with ratios > 2 and dogs with ratios ≤ 2 did not differ significantly with regard to sex, clinical group, reproductive status, or age. CONCLUSIONS AND CLINICAL RELEVANCE: Determination of the U:UH(2) concentration ratio was easy to perform. Ratios were variable among dogs, possibly suggesting differences in dihydropyrimidine dehydrogenase activity. However, studies correlating U:UH(2) concentration ratio and fluoropyrimidine antimetabolite drug tolerability are required to further evaluate the test's validity and its appropriate use in dogs.